Pilot Study of Subcutaneous Amifostine in Patients Undergoing Postoperative Intensity Modulated Radiation Therapy for Head and Neck Cancer: Preliminary Data

The major salivary glands produce about 90% of salivary secretions; the minor salivary glands produce the remainder. Standard conventional radiation therapy for advanced oropharyngeal tumors typically involves administering high radiation dose to the major salivary glands bilaterally. In most cases, this causes a marked reduction in oral saliva output. Xerostomia is the most prevalent late side effect of radiation for head and neck malignancies and is cited by patients as the major cause of decreased quality of life. The degree of xerostomia has been reported to depend on the radiation dose and salivary gland volume irradiated. Several studies show dose volume response relationships in the salivary glands, suggesting the possibility of significant improvement in saliva production post radiation as well as quality of life if radiation techniques can spare the salivary glands. In recent years, conformal radiation techniques have evolved, which may allow radiation of tumor targets in the head and neck area while sparing substantial portions of salivary glands. It has been shown that in using these techniques, adequate irradiation of the targets while sparing major salivary glands is feasible. Early clinical experience showed substantial sparing of salivary flow following radiation and suggested an improvement of tumor control and of xerostomia over that achieved with standard radiation techniques. We hypothesize that the addition of a radioprotector may further improve salivary function over that obtained with intensity modulated radiation therapy alone. To test this hypothesis, we initiated a pilot clinical trial whose principal objective is to compare measurements of unstimulated and stimulated salivary flow rates 6 months after intensity modulated radiation therapy plus amifostine (Ethyol; MedImmune, Inc, Gaithersburg, MD) (study patients) with those obtained in historical controls treated with intensity modulated radiation therapy alone.